tbuckley/cabot-search huggingface dataset:
Abstract 54: Newly Initiation of Antihypertensive Medication on Reduction of Incident Dementia: Emulation of Target Trials Based on the Health and Retirement Study
Authors: Jingkai Wei, Hanzhang Xu, Donglan Zhang, Huilin Tang, Tiansheng Wang, Susan E Steck, Jiajia Zhang, Jasmin Divers, Anwar T Merchant
Journal: Circulation (2023)

Background: Although antihypertensive medication use is associated with a lower risk of dementia in observational studies, such an effect is rarely found in randomized controlled trials (RCTs). As midlife high blood pressure is more predictive of incident dementia than hypertension in late life, so midlife hypertension may be the target for intervention. However, no such an RCT has been conducted to prevent incident dementia through reducing high blood pressure from midlife. Therefore, we aimed to emulate a target trial with an observational study design to estimate the effect of initiating antihypertensive medication from midlife on reducing incident dementia. Hypothesis: We assessed the hypothesis that newly initiating antihypertensive medication among midlife adults with hypertension reduces incident dementia. Methods: New-user design was used to emulate a target trial using data from the Health and Retirement Study from 1996 to 2018 with non-institutional dementia-free participants aged 45 to 65 years without taking antihypertensive medication in past two years. Participants with information of self-reported hypertension diagnosis and new use of antihypertensive medication, as well as no dementia based on algorithm were included in the analysis and represented group with/without initiating antihypertensive medication. An intention-to-treat approach was applied for analysis, and sequential emulation was used to increase the efficiency of intention-to-treat analysis. Proportional hazards models were applied to estimate the effect of initiating antihypertensive medication on incident dementia. Inverse probability of treatment and censoring weights were created to adjust for confounding and selection bias due to loss to follow-up, and death was considered as a competing event. Another emulated target trial with the same specifications was conducted among late-life adults aged 66 years or older for comparison. Results: A total of 3,151 non-unique participants (baseline mean age: 59.0 ± 4.0 years, 54.6% (n=1,719) women, 78.3% (n=2468) Whites, 71.4% (n=2,249) initiating antihypertensive medication) were included in the analysis. Initiating antihypertensive medication showed benefit in reducing incident dementia over a total of 22-year follow-up, with a reduction of risk by 19% (hazards ratio=0.81, 95% confidence interval: 0.66, 0.99). No significant reduction was observed for initiators of antihypertensive medication from late life. Conclusions: Initiating antihypertensive medication from midlife, but not from late life may reduce incident dementia. Future studies are warranted to estimate the effect of blood pressure lowering in midlife through other means of intervention in reducing incident dementia.
Abstract P396: A Culturally Tailored Mobile Health Lifestyle Intervention Improves Cardiovascular Health Among African Americans With Preexisting Risk Factors
Authors: Mathias Lalika, Sarah Jenkins, Sharonne N Hayes, Clarence Jones, Lora E Burke, Lisa A Cooper, Christi Patten, LaPrincess C Brewer
Journal: Circulation (2023)

Background: African-American (AA) adults have a higher prevalence of cardiovascular (CV) risk factors, leading to higher CV disease mortality than White adults. Prior findings of our mobile health (mHealth) lifestyle intervention (FAITH! App) demonstrated efficacy in promoting ideal cardiovascular health (CVH) in AAs. Hypothesis: We hypothesized that the intervention group with preexisting CV risk factors would have a greater increase in LS7 scores than the control group with the same risk factors following use of the FAITH! App. Methods: A cluster randomized controlled trial was conducted among AAs from 16 churches in Minnesota. The intervention included culturally relevant, LS7-focused education modules, diet/physical activity self-monitoring and a group sharing board. A subgroup of participants with ≥1 diagnosis of overweight/obesity, hyperlipidemia, hypertension (HTN) or diabetes was examined. The primary outcome was change in LS7 score—a measure of CVH ranging from poor to ideal (range 0-14 points)—at 6 months post-intervention. Results: Forty-nine participants (75.5% female) were included in the intervention (n=20; mean age [SD]: 58.8 [9.5]) or control (n=29, mean age [SD]: 52.5 [10.7]) groups (Table 1). There was no significant difference in the CV risk factor prevalence between the two groups. There was a greater increase in LS7 score in the intervention vs. control group across all CV risk factors, with significant differences among those with overweight/obesity (1.77, p&lt;.0001) and with 2+ or 3+ CV risk factors (1.00, p=.03; 1.09, p=.04). Compared to the control group, the increase in the percentage of participants with ideal LS7 scores in the intervention group was higher among those with overweight/obesity, HTN, diabetes and 3+ CV risk factors. Conclusions: Our culturally tailored mHealth lifestyle intervention was associated with notable increases in LS7 scores among AAs with preexisting CV risk factors, suggesting its efficacy in improving CVH among this population.
Abstract P327: Device-Measured Sedentary Behavior and Risk of 1-Year Hospital Readmission After Suspected Acute Coronary Syndrome
Authors: Benjamin D Boudreaux, Chang Xu, Gabriel Sanchez, Margaret Murdock, Gaspar Cruz, Ammie Jurado, Andrea T Duran, Ian M Kronish, Donald Edmondson, Keith Diaz
Journal: Circulation (2023)

Background: Patients hospitalized with acute coronary syndrome (ACS) have an increased risk of a readmission during the first year after discharge; necessitating a need to identify modifiable therapeutic targets to improve outcomes. While moderate to vigorous physical activity (MVPA) has been a hallmark of secondary prevention efforts to prevent hospital readmission, sedentary behavior (SB) has emerged as a potentially unique and clinically important aspect of the physical activity profile. Yet, little is known regarding whether SB is associated with hospital readmission in ACS patients independent from or in addition to MVPA levels. Purpose: To examine the association between device-measured SB and risk of 1-year hospital readmission among patients evaluated for ACS, independent of MVPA. Methods: Patients (n=603, 47.8% female, 62.5±13.0 yrs) evaluated in the emergency department for ACS were fitted with a GENEActiv accelerometer in-hospital and were instructed to wear the device on their non-dominant wrist continuously in-hospital and for 30 days post-discharge. Hospital readmissions were ascertained by proactively searching medical records for any possible hospitalizations and by contacting participants or their closest contacts at 1- and 12-months follow-up; with supporting documentation secured from hospital medical records. Results: Over 1-year follow-up, 281 (46.6%) patients were readmitted. SB was associated with increased risk of 1-year hospital readmission after adjusting for socio-demographic factors, comorbidities, and disease severity indicators [HR per 1-hour per day increase in SB= 1.09, 95% CI: 1.01, 1.18]. The association remained significant after further adjusting for MVPA [HR per 1-hour per day increase in SB= 1.11, 95% CI: 1.02, 1.22]. In joint association analyses, high sedentary time in combination with low MVPA was associated with the greatest risk of 1-year hospital readmission in a fully adjusted model (HR: 2.18; 95%: CI: 1.44, 3.31) compared to the referent group (low SB/high MVPA). However, even among participants with higher levels of MVPA; high sedentary time was associated with a greater risk of 1-year re-hospitalization (HR: 1.54; 95% CI: 1.05, 2.27). For participants with low MVPA and low sedentary time, no significant association was observed (HR: 1.37; 95% CI: 0.84, 2.21). Conclusions: SB was associated with an increased risk of 1-year hospital readmission among patients evaluated for ACS. This increased risk was independent of MVPA and was not eliminated by high levels of MVPA. Implications of this study suggest that reducing SB should be considered as a modifiable therapeutic target in addition to MVPA to improve outcomes in ACS survivors.
Abstract P551: Genetic Variants in the Adenosine Triphosphate-Binding Cassette Transporter A1 and Risk of Age-Related Macular Degeneration
Authors: Liv Nordestgaard, Mette Christoffersen, Shoaib Afzal, Borge G Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Journal: Circulation (2023)

Objective: Genetic variants in the adenosine triphosphate-binding cassette transporter A1( ABCA1 ) is associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. Methods: We genotyped all amino acid changing ABCA1 variants with a minor allele frequency above 0.002, measured plasma HDL cholesterol and other plasma lipids, and used Cox regression to assess risk of AMD. We created an HDL cholesterol weighted allele score and tested the association with risk of AMD on a continuous scale and in tertiles. Further, we performed mediation analyses. Main outcome measures: 1,554 AMD events. Median follow-up of 10 years. Results: Of 90,344 study participants, 55% were women. Median age was 58 (interquartile range: 47-67) years. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, dry AMD, and wet AMD both in an age- and sex adjusted model and in a multivariable adjusted model (See Figure). The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14-1.49) for all-cause AMD, 1.26 (1.06-1.50) for dry AMD, and 1.31 (1.12-1.53) for wet AMD in a multivariable adjusted model. 6-8% of the effect was mediated through HDL cholesterol. There was no interaction between weighted allele score tertiles and confounding factors on risk of AMD. Conclusions: Amino acid changing genetic variants in ABCA1 which were associated with higher HDL cholesterol concentrations, were also associated with higher risk of AMD, both on a weighted allele score continuously and when divided into tertiles.
Abstract 36: Life’s Essential 8 and Life Expectancy Among Adults in the United States
Authors: Hao Ma, Xuan Wang, Qiaochu Xue, Xiang Li, Zhaoxia Liang, Yoriko Heianza, Oscar Franco, Lu Qi
Journal: Circulation (2023)

Background: Cardiovascular disease (CVD) may be the main reason for stagnant growth in life expectancy in the US since 2010. The American Heart Association (AHA) recently released updated algorithm for evaluating cardiovascular health (CVH)--life’s essential 8 (LE8) score. Hypothesis: We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults. Methods: We included 23003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2005-2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. Life table method was used to estimate life expectancy by levels of the CVH. The cause-specific decomposition of the life expectancy differences was evaluated by the Arriaga’s method. Results: During a median of 7.8 years of follow-up, 1359 total deaths occurred (772 in men and 587 in women). The estimated life expectancy at age 50 was 25.5 years (95% CI, 23.8-27.2), 31.2 years (95% CI, 30.4-31.9) and 33.1 years (95% CI, 29.8-36.2) in men with poor, intermediate and ideal CVH, respectively. The corresponding estimated life expectancy at age 50 in women was 29.5 years (95% CI, 27.8-31.1), 34.2 years (95% CI, 33.5-34.9) and 38.4 years (95% CI, 35.4-41.0), respectively. Equivalently, men and women with ideal CVH had an average 7.5 (95% CI, 3.5-11.5) and 8.9 (95% CI, 5.2-12.5) more years of life expectancy at age 50, respectively, compared with their counterparts with poor CVH. In men, on average, 41.8 % of the gained life expectancy at age 50 from adhering to ideal CVH was attributable to reduced CVD death. The corresponding percentage was 44.1 % in women. Similarly significant associations of CVH with life expectancy were observed in Non-Hispanic Whites and Non-Hispanic Blacks but not in Mexican Americans. Conclusions: Adhering to an ideal CVH, defined as the LE8 score, is related to a considerably increased life expectancy in the US adults.
Abstract P582: Race, Social Determinants of Health, and Comorbidity Patterns Among Participants With Heart Failure in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Ene M Enogela, Parag Goyal, Monika M Safford, Stephen Clarkson, Thomas W Buford, Elizabeth A Jackson, Todd Brown, Leann Long, Raegan W Durant, Emily B Levitan
Journal: Circulation (2023)

Introduction: Heart failure (HF) is often accompanied by comorbid conditions that impact outcomes. We examined racial differences in comorbidities among patients with HF and the mediating role of social determinants of health (SDOH). Hypothesis: Comorbidities among people hospitalized with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) will differ by race, and SDOH will partly explain the disparities. Methods: Black and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 (n = 506 HFpEF and 742 HFrEF, 4.1% of the REGARDS cohort) were included in this cross-sectional analysis. Comorbidities were abstracted from HF hospitalization records. We estimated age- and sex-adjusted prevalence ratios (PR) for comorbidities comparing Black to White participants. Guided by the Healthy People’s 2030 framework, SDOH including income, education, marital status, rural residence, ZIP code-level poverty, healthcare provider shortage area and poor public infrastructure were considered as potential mediators using the inverse odds weighting method. Results: Among participants with a HF hospitalization, the median age was 79 (IQR: 73 – 85) years and 74 (67 – 80) years for White and Black adults, respectively. There were racial differences in the prevalence of some comorbidities between Black and White participants (Table). In HFpEF, low income and education explained 27% of the excess diabetes experienced by Black adults compared to White adults (P &lt; 0.05). There was no significant mediation of other associations by SDOH. Conclusions: There were racial differences in the patterns of comorbidities among REGARDS participants with HF, with low income and education partly explaining the higher prevalence of diabetes among Black adults with HFpEF.
Abstract P389: Sex-Specific Genetic Interrogation of Cardiovascular Disease Drug Targets
Authors: Marie-Joe Dib, Devendra Meena, Loukas Zagkos, Gill Dipender, Paul Elliott, Abbas Dehghan, Ioanna Tzoulaki
Journal: Circulation (2023)

Investigating sex-specific effects of genetically-proxied drug target inhibition on cardiovascular disease (CVD) liability may improve the understanding of CVD pathophysiology and therapeutic intervention, to enhance the formulation of sex-specific treatment in clinical practice. We aimed to investigate sex-specific associations between genetic variation at CVD drug targets and CVD risk factors in the UK Biobank for anti-hypertensive, lipid-lowering and anti-inflammatory drug targets. Firstly, we conducted genome-wide association studies (GWAS) for systolic blood pressure (SBP), C-reactive protein (CRP), low density lipoprotein (LDL)-cholesterol for 488,226 women and men in the UK Biobank. We then performed genetic colocalization analyses to identify shared or differential genetic loci for CVD risk factors in males and females. Our findings highlight that females and males share potentially causal variants for SBP at the ADRB1, CACNA1D, CACNB2, CACNB3 and SLC12A3 drug targets, for LDL-cholesterol at PCSK9, HMGCR, and for CRP at IL6R . Notably, we highlight heterogeneous effects of SBP in men and women at ACE, CACNA1S, CACNA1C . This is the first comprehensive genetic interrogation of sex-specific effects on drug targets, suggesting physiological differences in hypertension-mediated CVD between men and women and potential differential response to anti-hypertensive medication. Whether this has viable clinical implications is yet to be formally tested in further sex-specific analyses in genetic association studies and clinical trials.
Abstract P272: Spatial and Temporal Trends of Infective Endocarditis Hospitalizations in Kentucky, 2008-2018
Authors: Meera Marji, Jay christian, Steven Browning, Steve W Leung, Richard Charnigo, Anna Kucharska-Newton
Journal: Circulation (2023)

Background: Infective endocarditis (IE) hospitalization rates have increased significantly in the last decade, primarily due to the opioid abuse epidemic. A North Carolina study showed an increase in intravenous drug use infective endocarditis (IDU-IE) from 0.9 to 10.9/100,000 during 2007-2017. In 2016, Kentucky ranked among the top ten states with the highest opioid-related overdose deaths. Limited data about IE trends are available for Kentucky. Objective: To examine county-level spatial and temporal trends in IE rates in Kentucky and identify significant high-rate clusters. Methods: We used the Kentucky hospital inpatient discharge data (2008-2018). We included hospitalizations for patients 18 years and older who are Kentucky residents. All IE admissions were identified using ICD-9 and ICD-10 diagnosis codes (421.0, 421.1, 421.9, 424.90, 424.91, 424.99, 112.81, I33.0, I39, I33.9, I38, A3282, and B376). IDU-IE were identified using additional ICD codes for injected illicit drug use. We used US Census data to calculate yearly hospitalization rates of IE /100,000 residents. Joinpoint regression was used to calculate annual percent change (APC). We conducted spatiotemporal cluster analysis at the county level using a Poisson model in SaTScan. Results: Throughout the study period, there were 17,787 IE hospital admissions, including 3,577 IDU-IE. Medicaid patients were more often in the IDU-IE group rather than the non-IDU-IE (71% versus 15%). The IDU-IE hospitalization rate increased from 1.2 to 27.3 / 100,000 in 2008 to 2018 (Figure). From 2013 to 2018, APC for IDU-IE hospitalizations was 71.3, (95% CI: 47.8, 98.5). The spatiotemporal scan statistics identified five statistically significant clusters. The largest cluster occurred during 2015-2018 and included 34 counties out of 120 Kentucky counties, all located in the Appalachian region of Eastern Kentucky (RR= 2.1, p&lt;0.00001). Conclusion: Our study showed increased rates of IE hospitalizations due to an increase in IDU-IE, especially in Eastern Kentucky.
Abstract P663: Significantly Slower Progression of Aortic Calcification Among Japanese in Japan Than White and Japanese Americans in a Multiethnic Cohort of Middle-Aged Men - ERA JUMP (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort) Study
Authors: Mengyi Li, Akira Fujiyoshi, Bradley Willcox, Jiatong Li, Aya Kadota, Sayaka Kadowaki, Takashi Kadowaki, Yuefang Chang, Katsuyuki Miura, Daniel Edmundowicz, Tomonori Okamura, Kamal Masaki, Hirotsugu Ueshima, Akira M Sekikawa
Journal: Circulation (2023)

Background: Calcification of the aorta is a biomarker of atherosclerosis and a predictor of cardiovascular morbidity and mortality. Low mortality from coronary heart disease in Japan cannot be fully explained by genetics or traditional risk factors. Our objective was to compare the progression of aortic calcification (AC) between Japanese in Japan, white Americans, and third-generation Japanese Americans without ethnic admixture in population-based samples of middle-aged men from the ERA JUMP cohort and to examine whether the higher blood levels of marine omega–3 fatty acids (OM3) in Japanese in Japan than in Americans account for the difference. Method: Men (n=700) aged 40-49 years (252 Japanese in Japan, 238 white Americans, and 210 Japanese Americans) were examined at baseline and 4-7 years later. AC was evaluated from the aortic arch to the iliac bifurcation with computed tomography. AC score was assessed with the Agatston method. Progression of AC score was calculated as the difference between the follow-up and baseline of the natural log-transformed AC+1. Robust linear regression models were used to compare the progression of AC and multivariable logistic regression models were fitted to compare the incidence of AC (AC≥50 at follow-up) among those with baseline AC&lt;50. Results: Japanese in Japan had a significantly slower progression and lower incidence of AC compared to white and Japanese Americans after adjusting for age, baseline AC score, follow-up time, and traditional risk factors. Median blood levels of OM3 were 7.9% for Japanese in Japan, 2.6% for white Americans and 3.8% for Japanese Americans. Additional adjustment for OM3 did not account for the significant difference in AC progression but accounted for the difference in incidence between Japanese in Japan and Japanese Americans (Table 1). Conclusion: Japanese in Japan had a significantly slower progression and lower incidence of AC compared to white and Japanese Americans. Higher OM3 in Japanese in Japan partly accounted for the difference in incidence.